Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.

Proprotein convertases (PCs) is a protein family which includes nine highly specific subtilisin-like serine endopeptidases in mammals. The system of PCs is involved in carcinogenesis and levels of PC mRNAs alter in cancer, which suggests expression status of PCs as a possible marker for cancer typing and prognosis. The goal of this work was to assess the information value of expression profiling of PC genes. Quantitative polymerase chain reaction was used for the first time to analyze mRNA levels of all PC genes as well as matrix metalloproteinase genes MMP2 and MMP14, which are substrates of PCs, in 30 matched pairs of samples of human lung cancer tumor and adjacent tissues without pathology. Significant changes in the expression of PCs have been revealed in tumor tissues: increased FURIN mRNA level (p<0.00005) and decreased mRNA levels of PCSK2 (p<0.007), PCSK5 (p<0.0002), PCSK7 (p<0.002), PCSK9 (p<0.00008), and MBTPS1 (p<0.00004) as well as a tendency to increase in the level of PCSK1 mRNA. Four distinct groups of samples have been identified by cluster analysis of the expression patterns of PC genes in tumor vs. normal tissue. Three of these groups covering 80% of samples feature a strong elevation in the expression of a single gene in cancer: FURIN, PCSK1, or PCSK6. Thus, the changes in the expression of PC genes have a limited number of scenarios, which may reflect different pathways of tumor development and cryptic features of tumors. This finding allows to consider the mRNAs of PC genes as potentially important tumor markers

Description of the specimens studied and heat map presentation of the ratio values of gene expression in tumor vs. adjacent tissues without histological pathology.

<p>SCC, squamous cell lung carcinoma; AdC, adenocarcinoma; AdC/SCC, both AdC and SCC cells were found in the tumor tissue; SCLC, small cell lung carcinoma; P, peripheral tumor location; C, central tumor location; Y, tumor with keratinization; N, tumor without keratinization; ‘-’, no data. The heat map is shown in log₂ scale. Gray cells indicate specimens with undetectable mRNA in both tumor and normal tissues.</p

Correlations between expression profiles of the genes studied.

*<p>R_s is Spearman correlation coefficient (p<0.05).</p

Clustering of PC genes' expression data.

<p>Specimens numbering corresponds to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055752#pone-0055752-g001" target="_blank">Fig. 1</a>. The Ratio^T/N values in the heat map were row-normalized and shown in linear scale. Gray cells indicate specimens with undetectable mRNA in both normal and cancer tissues. Branch length reflects the distance between the dendrogram nodes. The clusters found are marked as C1, C2, C3 and C4.</p

Gene designations and TaqMan Gene Expression Assays used in real-time PCR.

*<p>HGNC – HUGO Gene Nomenclature Committee (<a href="http://www.genenames.org" target="_blank">www.genenames.org</a>).</p